Investigating Reading Enjoyment in Adults With Dyslexia.

Previous studies have suggested that adults with dyslexia do not enjoy reading, based on data from trait-based questionnaires. This study uses state-based measures of reading to offer greater insight into different aspects of motivation, including liking and wanting. In a new paradigm sensitive to dynamic changes in reading enjoyment, adults with dyslexia (n = 59) and without dyslexia (n = 59) read 24 book extracts, rated their enjoyment and answered a question about the extract.

Regorafenib induces DNA damage and enhances PARP inhibitor efficacy in pancreatic ductal carcinoma.

Background: There is increasing interest in enhancing the response of the PARP inhibitor olaparib, which is currently approved for pancreatic ductal adenocarcinoma (PDAC) patients with defects in DNA damage repair associated with germline BRCA1/2 mutations. Moreover, agents that can mimic these defects in the absence of germline BRCA1/2 mutations are an area of active research in hopes of increasing the number of patients eligible for treatment with PARP inhibitors. The extent to which regorafenib, an FDA-approved tyrosine kinase inhibitor, can be used to enhance the efficacy of PARP inhibitors in PDAC cells without known BRCA1/2 mutations remains to be investigated.

Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells.

Despite advances in immune checkpoint inhibitors, chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX [5-fluorouracil, F; irinotecan, I; and oxaliplatin, O (FIO)] regimen, and immune checkpoint inhibitors have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in patients with PDAC. In this study, we report that neoadjuvant FOLFIRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation.

Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer.

MRTX1133 is currently being evaluated in patients with pancreatic ductal adenocarcinoma (PDAC) tumors harboring a KRASG12D mutation. Combination strategies have the potential to enhance the efficacy of MRTX1133 to further promote cell death and tumor regression. In this study, we demonstrated that MRTX1133 increased the levels of the proapoptotic protein BIM in PDAC cells and conferred sensitivity to the FDA-approved BCL2 inhibitor venetoclax.

BET Inhibition Rescues Acinar-Ductal-Metaplasia and Ciliogenesis and Ameliorates Chronic Pancreatitis-Driven Changes in Mice With Loss of the Polarity Protein Par3.

Background & Aims: The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar pancreas injury and regeneration are poorly understood.

Methods: Cerulein-induced pancreatitis was induced in mice with conditional deletion of the polarity protein Par3 in the pancreas.

Effects of Airway Localization Device Use During Surgical Cricothyrotomy on Procedural Times and Confidence Levels of Pre-Hospital Personnel.

This study evaluated the effect of an airway localization device (ALD) on surgical cricothyrotomy (SC) success rates and prehospital provider confidence. SC is indicated in 0.62% to 1.

Using a willingness to wait design to assess how readers value text.

What affects moment-to-moment motivation to read? Existing reading motivation questionnaires are trait-based and not well suited to capturing the dynamic, situational influences of text or social context. Drawing on the decision science literature, we have created a paradigm to measure situational enjoyment during reading. Using this paradigm, we find reading enjoyment is associated with further decision-making about the text and with reading comprehension.

High-throughput phenogenotyping clinical strains reveals bacterial determinants of treatment outcomes.

Background: Combatting the tuberculosis (TB) epidemic caused by ( ) necessitates a better understanding of the factors contributing to patient clinical outcomes and transmission. While host and environmental factors have been evaluated, the impact of genetic background and phenotypic diversity is underexplored. Previous work has made associations between genetic lineages and some clinical and epidemiological features, but the bacterial traits underlying these connections are largely unknown.

Theoretical understanding of evolutionary dynamics on inhomogeneous networks.

Evolution is the main feature of all biological systems that allows populations to change their characteristics over successive generations. A powerful approach to understand evolutionary dynamics is to investigate fixation probabilities and fixation times of novel mutations on networks that mimic biological populations. It is now well established that the structure of such networks can have dramatic effects on evolutionary dynamics.

Predictors of Clinical Success After Transcatheter Paravalvular Leak Closure: An International Prospective Multicenter Registry.

Background: Transcatheter closure of a symptomatic prosthetic paravalvular leak (PVL) is feasible, but there is presently no conclusive evidence to show consistent efficacy. We aimed to identify predictors of clinical success after transcatheter PVL closure.

Methods: Consecutive patients referred to 24 European centers for transcatheter PVL closure in 2017 to 2019 were included in a prospective registry (, FFPP).

The role of spatial structures of tissues in cancer initiation dynamics.

It is widely believed that biological tissues evolved to lower the risks of cancer development. One of the specific ways to minimize the chances of tumor formation comes from proper spatial organization of tissues. However, the microscopic mechanisms of underlying processes remain not fully understood.

Emergency vs Delayed Coronary Angiogram in Survivors of Out-of-Hospital Cardiac Arrest: Results of the Randomized, Multicentric EMERGE Trial.

Importance: Although an emergency coronary angiogram (CAG) is recommended for patients who experience an out-of-hospital cardiac arrest (OHCA) with ST-segment elevation on the postresuscitation electrocardiogram (ECG), this strategy is still debated in patients without ST-segment elevation.

Objective: To assess the 180-day survival rate with Cerebral Performance Category (CPC) 1 or 2 of patients who experience an OHCA without ST-segment elevation on ECG and undergo emergency CAG vs delayed CAG.

Design, Setting, And Participants: The Emergency vs Delayed Coronary Angiogram in Survivors of Out-of-Hospital Cardiac Arrest (EMERGE) trial randomly assigned survivors of an OHCA without ST-segment elevation on ECG to either emergency or delayed (48 to 96 hours) CAG in 22 French centers.